2019-01-21T23:18:02ZA novel interventional guidance framework for transseptal puncture in left atrial interventionshttp://hdl.handle.net/1822/58231
Título: A novel interventional guidance framework for transseptal puncture in left atrial interventions
Autor: Morais, Pedro André Gonçalves; Vilaça, João Luís Araújo Martins; Queirós, Sandro Filipe Monteiro; Rodrigues, Pedro Miguel Loureiro; Tavares, João Manuel R. S.; D’hooge, Jan
Resumo: Access to the left atrium is required for several percutaneous cardiac interventions. In these procedures, the inter-atrial septal wall is punctured using a
catheter inserted in the right atrium via the venous system under image guidance.
Although this approach (termed transseptal puncture - TSP) is performed daily,
complications are common. Moreover, the exact location at which the septum needs
to be traversed is determined entirely based on the interventionist’s experience,
which is sub-optimal. In this work, we present a novel concept for the development
of an interventional guidance framework for TSP. The pre-procedural planning
stage is fused with 3D intra-procedural images (echocardiography) using manually
defined landmarks, transferring the relevant anatomical landmarks to the interventional space and enhancing the echocardiographic images. In addition, electromagnetic sensors are attached to the surgical instruments, tracking them and allowing
the inclusion of their spatial position in the enhanced intra-procedural world. Two
patient-specific atrial phantom models were used to evaluate this framework. One
operator performed the planning, calibrated the setup and performed the puncture.
To assess the framework’s accuracy, a metallic landmark was positioned in the
punctured location and compared with the ideal one. The intervention was possible
in both models, but in one case positioning of the landmark failed. An error of approximately of 6 mm was registered for the successful case. Technical characteristics of the framework showed an acceptable performance, with a frame rate ~5
frames/sec. The manual calibration setup required ~60 min. This study presented a
proof-of-concept for an interventional guidance framework for TSP. However, a
more automated solution and further studies to assess its accuracy are required.
<b>Tipo</b>: conferencePaperRole of deficits in pathogen recognition receptors in infection susceptibilityhttp://hdl.handle.net/1822/58097
Título: Role of deficits in pathogen recognition receptors in infection susceptibility
Autor: Cunha, Cristina; Gonçalves, Samuel Martins; Carvalho, Agostinho
<b>Tipo</b>: bookPart2019-01-11T16:08:56ZHost genetic signatures of susceptibility to fungal diseasehttp://hdl.handle.net/1822/58095
Título: Host genetic signatures of susceptibility to fungal disease
Autor: Campos, Cláudia F.; Veerdonk, Frank L. van de; Gonçalves, Samuel Martins; Cunha, Cristina; Netea, Mihai G; Carvalho, Agostinho
Resumo: Our relative inability to predict the development of fungal disease and its clinical outcome raises fundamental questions about its actual pathogenesis. Several clinical risk factors are described to predispose to fungal disease, particularly in immunocompromised and severely ill patients. However, these alone do not entirely explain why, under comparable clinical conditions, only some patients develop infection. Recent clinical and epidemiological studies have reported an expanding number of monogenic defects and common polymorphisms associated with fungal disease. By directly implicating genetic variation in the functional regulation of immune mediators and interacting pathways, these studies have provided critical insights into the human immunobiology of fungal disease. Most of the common genetic defects reported were described or suggested to impair fungal recognition by the innate immune system. Here, we review common genetic variation in pattern recognition receptors and its impact on the immune response against the two major fungal pathogens Candida albicans and Aspergillus fumigatus. In addition, we discuss potential strategies and opportunities for the clinical translation of genetic information in the field of medical mycology. These approaches are expected to transfigure current clinical practice by unleashing an unprecedented ability to personalize prophylaxis, therapy and monitoring for fungal disease.
<b>Tipo</b>: bookPartEvaluating the Role of Host AMPK in Leishmania Burdenhttp://hdl.handle.net/1822/58081
Título: Evaluating the Role of Host AMPK in Leishmania Burden
Autor: Moreira, Diana Raquel Bento; Estaquier, Jérôme; Cordeiro-da-Silva, Anabela; Silvestre, Ricardo Jorge Leal
Resumo: The study of host AMP-activated protein kinase (AMPK) activation during Leishmania infection imposes distinct types of techniques to measure protein expression and activation, as well as to quantify, at transcription and translational levels, its downstream targets. The investigation of host AMPK protein modulation during Leishmania infection should primarily be assessed during in vitro infections using as a host murine bone marrow-derived macrophages (BMMos). The infection outcome is assessed measuring the percentage of infected cells in the context of BMMos. To evaluate AMPK activity during infection, the expression of AMPK phosphorylated at Thr172 as well as the transcription and translational levels of its downstream targets are evaluated by quantitative PCR and immunoblotting. The modulation of AMPK activity in vivo is determined specifically in sorted splenic macrophages harboring Leishmania parasites recovered from infected mice using fluorescent-labeled parasites in the infectious inocolum. The modulation of AMPK activity was assessed by AMPK activators and inhibitors and also using AMPK, SIRT1, or LKB1 KO mice models. The infection outcome in BMMos and in vivo was further determined using these two different approaches. To finally understand the metabolic impact of AMPK during infection, in vitro metabolic assays in infected BMMos were measured in the bioenergetic profile using an extracellular flux analyzer.
Descrição: Uncorrected proof
<b>Tipo</b>: bookPartPharmacological therapies for Machado-Joseph diseasehttp://hdl.handle.net/1822/57814
Título: Pharmacological therapies for Machado-Joseph disease
Autor: Silva, Sara Carina Duarte; Maciel, P.
Resumo: Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia type 3 (SCA3), is the most common autosomal dominant ataxia worldwide. MJD integrates a large group of disorders known as polyglutamine diseases (polyQ). To date, no effective treatment exists for MJD and other polyQ diseases. Nevertheless, researchers are making efforts to find treatment possibilities that modify the disease course or alleviate disease symptoms. Since neuroimaging studies in mutation carrying individuals suggest that in nervous system dysfunction begins many years before the onset of any detectable symptoms, the development of therapeutic interventions becomes of great importance, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset. Potential therapeutic targets for MJD and polyQ diseases can be divided into (i) those that are aimed at the polyQ proteins themselves, namely gene silencing, attempts to enhance mutant protein degradation or inhibition/prevention of aggregation; and (ii) those that intercept the toxic downstream effects of the polyQ proteins, such as mitochondrial dysfunction and oxidative stress, transcriptional abnormalities, UPS impairment, excitotoxicity, or activation of cell death. The existence of relevant animal models and the recent contributions towards the identification of putative molecular mechanisms underlying MJD are impacting on the development of new drugs. To date only a few preclinical trials were conducted, nevertheless some had very promising results and some candidate drugs are close to being tested in humans. Clinical trials for MJD are also very few to date and their results not very promising, mostly due to trial design constraints. Here, we provide an overview of the pharmacological therapeutic strategies for MJD studied in animal models and patients, and of their possible translation into the clinical practice.
<b>Tipo</b>: bookPart2019-01-04T14:26:56Z